A multifaceted program is described which intends to expand our knowledge of the biochemistry and physiology of the neurotensin (NT) family of peptides. NT is a vasoactive, gut-contracting peptide originally isolated from extracts of bovine hypothalamic tissue and recently shown by radioimmunoassay (RIA) to be broadly distributed through the brain and alimentary canal of mammals, birds, reptiles, and crustacea. The physiological function (s) assigned to NT-like peptides is not known. In order to elucidate these functions and understand their evolution, a comparative analysis of the distribution and character of NT-variants in different life forms is planned. Human, chicken, and crustacean NT-like peptides will be isolated, biologically and chemically characterized, and synthesized. Their distributions will be mapped by RIA and immunohistochemical analyses will be performed. In the mammal, attempts will be made to manipulate plasma levels of radioimmunoassayable NT (R-NT) and to correlate them with physiological phenomena. One animal model will employ anti-NT antibody as a "trap" to capture R-NT appearing in the circulation. Several NT-affinity labeling reagents will be synthesized and employed to tag macromolecules involved in NT's synthesis, action(s), and degradation. Attempts will be made to induce and study a NT-deficiency syndrome using neutralizing antibody and NT-antagonists. Biosynthesis and release studies will be performed using brain and gut tissues. We will test the hypothesis that there exists in plasma a NT-generating system analogous to that for angiotensin. The ongoing studies of the NT-variants found in various bovine tissues will be continued by isolating NT-forms present in anterior pituitary tissue. Further characterization of R-NTs present in rabbit leukocytes and human synovial fluids will be performed.